External beam radiotherapy for unresectable hepatocellular carcinoma, an international multicenter phase I trial, SAKK 77/07 and SASL 26.

Herrmann, Evelyn; Naehrig, Diana; Sassowsky, Manfred; Bigler, Martin; Buijsen, Jeroen; Ciernik, Ilja; Zwahlen, Daniel; Pellanda, Alessandra Franzetti; Meister, Andreas; Brauchli, Peter; Berardi, Simona; Kuettel, Erika; Dufour, Jean-François; Aebersold, Daniel; Swiss Group for Clinical Cancer Research, SAKK (2017). External beam radiotherapy for unresectable hepatocellular carcinoma, an international multicenter phase I trial, SAKK 77/07 and SASL 26. Radiation oncology, 12(1), p. 12. BioMed Central 10.1186/s13014-016-0745-0

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PURPOSE To assess feasibility and safety of conventionally fractionated radiotherapy (cfRT) in patients with hepatocellular carcinoma (HCC). METHODS Patients with histologically confirmed stage cT1-4, cN0-1 HCC and Child-Pugh Score (CPS) A or B disease were included in a phase I multicenter trial. Metastatic HCC were allowed if ≥90% of total tumor volume was located within the liver. Patients were enrolled onto five dose-escalation levels (54-70Gy in 2Gy fractions) based on a modified 3 + 3 design, with cohorts of five patients instead of three patients in dose levels 4 and 5. Primary trial endpoint was dose-limiting toxicity (DLT), as specifically defined for 17 clinical and nine laboratory parameters as grade ≥3 or ≥4 toxicity (CTCAE vs. 3). The threshold to declare a dose level as maximum tolerated dose (MTD) was defined as a DLT rate of ≤16.7% in dose levels 1-3, and ≤10% in dose levels 4-5. Best objective response of target liver lesions and adverse events (AE's) were assessed as secondary endpoints. RESULTS The trial was terminated early in DL 3 due to low accrual. Nineteen patients were recruited. Fifteen patients were evaluable for the primary and 18 for the secondary endpoints. Maximum tolerated dose was not reached. One patient in dose level 1, and one patient in dose level 2 experienced DLT (lipase > 5xULN, and neutrophils <500/μL respectively). However, dose level 3 (62Gy) was completed, with no DLTs in 3 patients. Overall, 56% of patients had a partial response and 28% showed stable disease according to RECIST. No signs of radiation induced liver disease (RILD). Two patients in dose level 3 experienced lymphocytopenia grade 4, with no clinical impact. CONCLUSION Conventionally fractionated radiotherapy of 58Gy to even large HCC was safe for patients with CPS A and B. 62Gy was delivered to three patients without any sign of clinically relevant increased toxicity. The maximum tolerated dose could not be determined. TRIAL REGISTRATION ClinicalTrials.gov identifier NCT00777894 , registered October 21st, 2008.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Radiation Oncology
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Radio-Onkologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Radio-Onkologie

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Radiation Oncology > Medical Radiation Physics

UniBE Contributor:

Herrmann, Evelyn; Sassowsky, Manfred; Dufour, Jean-François and Aebersold, Daniel

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1748-717X

Publisher:

BioMed Central

Language:

English

Submitter:

Lilian Karin Smith-Wirth

Date Deposited:

17 Jul 2017 13:21

Last Modified:

23 Jul 2017 02:12

Publisher DOI:

10.1186/s13014-016-0745-0

PubMed ID:

28086942

Uncontrolled Keywords:

Conformal radiotherapy; Hepatocellular carcinoma; Liver; Radiation toxicity

BORIS DOI:

10.7892/boris.93534

URI:

https://boris.unibe.ch/id/eprint/93534

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